6-152430083-ATAG-A

Variant names:

• chr6-152430083-ATAG-A
• rs71659863
• NM_182961.4:c.4788+26_4788+28delCTA

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_182961.4(SYNE1):​c.4788+26_4788+28delCTA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 1,451,990 control chromosomes in the GnomAD database, including 16,016 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1833 hom., cov: 29)
  • Exomes 𝑓: 0.14 (14183 hom.)
• Consequence: SYNE1 NM_182961.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.30
• Publications: 3 publications found

Genes affected

SYNE1 (HGNC:17089): (spectrin repeat containing nuclear envelope protein 1) This gene encodes a spectrin repeat containing protein expressed in skeletal and smooth muscle, and peripheral blood lymphocytes, that localizes to the nuclear membrane. Mutations in this gene have been associated with autosomal recessive spinocerebellar ataxia 8, also referred to as autosomal recessive cerebellar ataxia type 1 or recessive ataxia of Beauce. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

SYNE1 Gene-Disease associations (from GenCC):

• autosomal recessive ataxia, Beauce type

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, G2P, Orphanet, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
• arthrogryposis multiplex congenita 3, myogenic type

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• Emery-Dreifuss muscular dystrophy 4, autosomal dominant

  Inheritance: AD Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Illumina
• autosomal dominant Emery-Dreifuss muscular dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• autosomal recessive myogenic arthrogryposis multiplex congenita

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 6-152430083-ATAG-A is Benign according to our data. Variant chr6-152430083-ATAG-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 262197.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNE1	NM_182961.4	c.4788+26_4788+28delCTA		intron_variant	Intron 36 of 145	ENST00000367255.10	NP_892006.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNE1	ENST00000367255.10	c.4788+26_4788+28delCTA		intron_variant	Intron 36 of 145	1	NM_182961.4	ENSP00000356224.5
SYNE1	ENST00000423061.6	c.4809+26_4809+28delCTA		intron_variant	Intron 36 of 145	1		ENSP00000396024.1
SYNE1	ENST00000461872.6	n.5006+26_5006+28delCTA		intron_variant	Intron 34 of 54	1
SYNE1	ENST00000367253.8	c.4788+26_4788+28delCTA		intron_variant	Intron 34 of 35	5		ENSP00000356222.4

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22667 AN: 151972 Hom.: 1831 Cov.: 29

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.144

GnomAD2 exomes AF: 0.151 AC: 30065 AN: 198550 AF XY: 0.153

Gnomad AFR exome AF: 0.164

Gnomad AMR exome AF: 0.0792

Gnomad ASJ exome AF: 0.124

Gnomad EAS exome AF: 0.379

Gnomad FIN exome AF: 0.169

Gnomad NFE exome AF: 0.129

Gnomad OTH exome AF: 0.129

GnomAD4 exome AF: 0.140 AC: 181889 AN: 1299902 Hom.: 14183 AF XY: 0.140 AC XY: 91285 AN XY: 650490

African (AFR) AF: 0.165 AC: 4964 AN: 30112

American (AMR) AF: 0.0863 AC: 3509 AN: 40662

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 2983 AN: 24650

East Asian (EAS) AF: 0.383 AC: 14424 AN: 37706

South Asian (SAS) AF: 0.165 AC: 13116 AN: 79506

European-Finnish (FIN) AF: 0.165 AC: 8474 AN: 51272

Middle Eastern (MID) AF: 0.110 AC: 536 AN: 4882

European-Non Finnish (NFE) AF: 0.129 AC: 125899 AN: 976566

Other (OTH) AF: 0.146 AC: 7984 AN: 54546

GnomAD4 genome AF: 0.149 AC: 22678 AN: 152088 Hom.: 1833 Cov.: 29 AF XY: 0.152 AC XY: 11298 AN XY: 74334

African (AFR) AF: 0.165 AC: 6869 AN: 41526

American (AMR) AF: 0.119 AC: 1826 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 441 AN: 3470

East Asian (EAS) AF: 0.367 AC: 1892 AN: 5158

South Asian (SAS) AF: 0.177 AC: 852 AN: 4816

European-Finnish (FIN) AF: 0.162 AC: 1706 AN: 10552

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.126 AC: 8590 AN: 67966

Other (OTH) AF: 0.142 AC: 299 AN: 2112

Alfa AF: 0.133 Hom.: 274

Bravo AF: 0.147

Asia WGS AF: 0.242 AC: 838 AN: 3454

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs71659863; hg19: chr6-152751218; COSMIC: COSV104533118; COSMIC: COSV104533118;